News:

ACE inhibitors (angiotensin converting enzyme inhibitors) have been shown to be particularly effective in protecting renal function of damaged kidneys, if there is significant proteinuria. They are more effective than other classes of hypotensive drug in the presence of proteinuria. This guidance also covers angiotensin receptor blockers (ARBs).

Patients who are likely to require particular caution and/or close supervision include those with:

severe heart failure - eg on high dose diuretic therapy which cannot be discontinued, or large doses of vasodilators

dehydration (e.g. caused by large fluid losses or diuretics)

hypotension (systolic BP less than 90 mmHg)

substantial renal impairment (e.g. creatinine over 300 micromol/l)

Before starting

You must know Urea, Creatinine, Potassium, Sodium values.

The major risks from ACE inhibitors are of hyperkalaemia and deterioration of (already) impaired renal function. The risks are greater in individuals with unsuspected renal artery stenosis.

Risk factors for hyperkalaemia and renal impairment

Peripheral vascular disease indicates a high risk of renal artery stenosis: other evidence of cardiovascular disease presents a moderate risk.

Pre-existing renal impairment

Old age

Which ACE inhibitor?

Captopril is the original agent but is short acting and has some additional side effects. Enalapril may be best administered twice daily. Many newer agents (eg. lisinopril, ramipril) can be given once daily, and may be less likely to cause first-dose hypotension. Benefits seem to be class effects, so choice of agent may be reasonably decided by convenience and cost. In general, the same considerations apply to therapy with angiotensin receptor blockers (ARBs).

Other drugs and diet

In patients with renal impairment, potassium-sparing diuretics and potassium supplements should usually be discontinued unless there is continuing hypokalaemia. If continued, monitoring for hyperkalaemia should be closer.

Witholding diuretics for 48h before commencing therapy will reduce the risk of first-dose hypotension. This is not usually necessary in simple hypertension but may be relevant in heart failure or renal failure requiring loop diuretics.

Non-steroidal anti-inflammatory drugs should be avoided if possible during the initiation phase.

The effects of ACE inhibition on blood pressure and proteinuria are potentiated by restriction of salt intake and by diuretics.

MODERATE AND HIGH RISK PATIENTS (see above) - check at 4 and 10 days. Checks should also be sent after dose increases, and if diuretic doses are increased.

For creatinine, a rise of over 20% is generally considered to be significant, but NICE/SIGN guidelines allow up to 30% rise (more info). Smaller rises are common and are to be expected in many patients.

For potassium, we suggest the following:

5 - 5.5

recheck in 7 days; may tolerate this if indication is strong

5.6 - 6.0

stop ACE inhibitor and check in 7 days

6.1 - 6.5

stop ACE inhibitor and check immediately

>6.5

stop ACE inhibitor and check urgently*

*seek hospital attention if these values are likely (or proved) to be real (eg non-haemolysed sample that reached the lab promptly)

For some patients, the value of ACE inhibitors is such that dietary restriction and acceptance of modest hyperkalaemia may be an acceptable course.

Dose titration

Increases can be made every week according to response, if you monitor the effects that frequently. We generally recommend a blood pressure target, although in patients with proteinuria there may be additional benefit from 'full dose' ACE inhibition even if the target blood pressures are achieved at a lower dose. See blood pressure targets in renal disease.

Side effects

Hyperkalaemia and renal impairment were mentioned above.

Cough is the most frequent side effect and is characteristically dry and troublesome. Try without the ACE inhibitor; if the problem is resolved, move on to an angiotensin II receptor antagonist (ARB) such as irbesartan, candesartan.

Angioedema is possibly under-diagnosed; it may occur long after starting the drug. ARBs are safe substitutes.

Alternative agents

Angiotensin II receptor blockers (ARBs) seem to share most of the benefits of ACE inhibitors on the kidneys and are an excellent alternative in case of ACE inhibitor-induced cough, or angioedema. However, like ACE inhibitors, they are prone to cause hyperkalaemia and impaired renal function.

Spironolactone has proteinuria-reducing properties, and a number of other agents are under investigation.